Over-patch having improved compatibility and a long adhesion duration and method for producing said over-patch

ABSTRACT

The invention relates to a medical product for a fastening duration of at least 7 days having good skin compatibility. The medical product includes a central adhesive compartment ( 3 ) and an over-patch. The over-patch is free of active ingredients and is formed from a water-vapor-permeable back layer ( 1 ) and an adhesive polymer layer ( 2 ) that is free of active ingredients. The invention further relates to a method for the production of the foregoing medical product, and to kits of parts containing laminates of layers  1  and  2.

The present invention relates to medical products which are worn on theskin and fastened by an overplaster. These products may be transdermaltherapeutic systems (ITS) which, besides the part containing activeingredient. additionally an active-ingredient-free overplaster, whichhas a specific construction, but also diagnostic agents or cannulaswhich are fixed by a plaster dressing. As is known, TTS are medicinalproducts in patch form which are adhered to the skin and are required todeliver at least one active ingredient over the entire administrationtime. It is obvious that these medical, properties must, adhere well,since otherwise there can be no delivery of active ingredient to theskin, the diagnostic agent does not work reliably, or the cannula slips.At the same time, instances of skin irritation must be prevented,meaning that the inherent tack of the TTS diagnostic agent or cannulafixing plaster may not be higher than is absolutely necessary.

Adhesive bonding, as is known, refers to the joining of two surfaces byan adhesive that connects the surfaces to one another through adhesionand cohesion. The adhesive here has to wet the respective surfaces. Itfollows from this that effective tack is governed not only by theadhesive but also by the nature of the surfaces. But different people,particularly with progressing age, have skins with different surfaces,with the individual skin types varying in their sensitivity of reactionto skin irritations. Although this requirement is familiar to the art,there are still no medical products which address this issue.

EP 1 992 363 discloses a transdermal patch having a backing layer and apressure-sensitively adhering layer, which in turn comprises an activeingredient reservoir layer and a layer which adheres on the skin. Theactive ingredient reservoir layer comprises a pressure-sensitiveacrylate adhesive, while the layer that adheres to the skin comprises astyrene-isoprene-styrene block copolymer.

DE 10 2004 038 285 A1 discloses a patch system for the release ofessential oils via the ambient air or transdermally without irritationto the mucosae or the skin. The patch system comprises a polymer matrixin which at least one essential oil is homogeneously distributed, asupport layer, and a removable protective layer. Additionally, there maybe a blockage layer impermeable to essential oils, apermeation-controlling membrane or a pressure-sensitive adhesive layerpresent.

Subject-matter of DE 10 2006 054 731 A1 is a transdermal therapeuticsystem for administering buprenorphine. This system comprises a backinglayer impermeable for the active ingredient, a matrix layer based onpolysiloxane or polyisobutylene, and comprising as well as buprenorphineat least one carboxylic acid, and a detachable protective layer.

Disclosed in EP 2 759 294 A1 is a patch for the transdermaladministration of fentanyl or a fentanyl homolog. The patch comprises abacking layer, a barrier layer, a pressure-sensitively adhering activeingredient layer, and a removable protective layer (release layer). Theactive-ingredient-containing layer contains fentanyl or a fentanylhomolog, an agent for improving the permeation of the fentanyl or thefentanyl homolog, and an acrylate adhesive. The acrylate adhesive iseither a nonfunctional polyacrylate adhesive or a polyacrylate adhesivewhich contains carboxyl groups.

Plasters of polyacrylates which can be utilized over a wear time of upto at least 7 days are known from U.S. 2009/0130130 A1, for example.Particularly when worn for a long time, plasters of this kind leadgenerally, on redetachment, to significant pain for spasmolytics,antihypertensives, psychopharmaceuticals, migraine agents, corticoids,analgesics, anticontraceptives, antirheumatics, anticholinergics,sympatholytics, sympathomimetics, vasodilators, anticoagulants andantiarthythmics.

Possible additions dependent on the polymer employed and on the activeingredient are plasticizers, tackifiers, stabilisers, carriers,diffusion- and penetration-regulating additions, or fillers. Thephysiologically unobjectionable substances contemplated are known.

The layer 2 may contain 0 to 5% (w/w) of a neutral oil, based, on thedry weight of this layer, as compatibilizer. Layer 2 may also contain0.5 to 5% (w/w) of dexpanthenol, based on the dry weight of this layer.

Layer may also comprise a non-amine-resistant polysiloxane polymers inwhich, after the polycondensation of the resin fraction and of thepolydimethylsiloxanol groups, the remaining silanol groups still freehave not been capped by methyl groups, to which 0 to 4% (w/w) ofsilicons oil are added, based on the dry weight of this layer.

Layer 2 may further comprise polyacrylates or vinyl-acrylate copolymerswhich have an acid number of less than 1.

Layer 2, finally, may also comprise styrene-isoprene-styrene blockcopolymers or styrene-butadiene-styrene block copolymers in combinationwith hydrogenated hydrocarbon resins and/or oils such as liquidparaffin.

In particular, the preferred TTS has the stated layers in each caseonce, and it consists preferably of the stated layers. The two statedpressure-sensitively adhering layers may be alike or different in termsof their polymer composition and/or thickness. The pressure-sensitivelyadhering polymer layer for application to the skin isoprene-styreneblock copolymers or styrene-butadiene-styrene block copolymers or thehomo- and/or copolymers thereof. The kit preferably comprises at leasttwo active-ingredient-free overplasters as defined and laminated onto anintermediate carrier, said overplasters differing in terms of thecomposition, of the layer 2, their size and/or their shape. With thispreferred embodiment, the user obtains a “construction kit” allowingthem to combine the compartment 3, manufactured in a standardizedprocess and meeting strict pharmaceutical stipulations, with a suitableoverplaster allowing the medical product to be used in accordance withthe requirements for a fixing time of at least 7 days and are the sametime meeting the requirements for good skin compatibility.

The invention further relates to a kit-of-parts comprising

-   -   at least two active-ingredient-free overplasters laminated onto        an intermediate carrier and composed of        -   a) a water vapor-permeable backing layer (1) and        -   b) a pressure-sensitively adhering, active-ingredient-free            polymer layer (2) comprising non-amine-resistant, highly            water vapor-permeable polysiloxanes, polyacrylates without            or only with few free acid groups, polyisobutylenes,            polybutylenes, styrene-isoprene-styrene block copolymers or            styrene-butadiene-styrene block copolymers or the homo-            and/or copolymers thereof,            where the overplasters differ in terms of the composition of            the layer 2, their size and/or their shape.

With this kit as well, the user obtains a “construction kit” allowingthem to combine the compartment 3, manufactured in a standardizedprocess and meeting strict pharmaceutical stipulations, with a suitableoverplaster, allowing the medical product to be utilised in accordancewith the requirements tor a fixing time of at least 7.

1. A medical product comprising a central compartment and anactive-ingredient-free overplaster, said overplaster comprising a) awater vapor-permeable backing layer and b) a pressure-sensitivelyadhering, active-ingredient-free polymer layer, wherein the centralcompartment is pressure-sensitively adhering and has direct skin contactafter removal of the a redetachable protective layer, the overplasterfixes the central compartment and overhangs the central compartment onall sides and the active-ingredient-free polymer layer comprisesnon-amine-resistant, highly water vapor-permeable polysiloxanes,polyacrylates or vinyl acetate-acrylate copolymers without free acidgroups or with an acid number of less than 1, polyisobutylenes,polybutylenes, styrene-isoprene-styrene block copolymers orstyrene-butadiene-styrene block copolymers.
 2. The medical product asclaimed in claim 1, wherein said medical product is a transdermaltherapeutic system (TTS) and the central compartment of comprises a) atleast one pressure-sensitively adhering, active-ingredient-containingpolymer layer which has direct skin contact after removal of theredetachable protective layer, and b) a separating layer which coversthe active-ingredient-containing polymer layer.
 3. The medical productas claimed in claim 1, wherein said product is a diagnostic agent andthe a diagnosis apparatus is located in the central compartment.
 4. Themedical product as claimed in claim 1, wherein said product is a cannulafixing plaster and the cannula is located in the central compartment. 5.The medical product as claimed in claim 1, wherein theactive-ingredient-free polymer layer comprises 0 to 5% (w/w) of aneutral oil, based on the layer dry weight, as compatibilizer.
 6. Themedical product as claimed in claim 1, wherein theactive-ingredient-free polymer layer comprises 0.5 to 5% (w/w) ofdexpanthenol, based on the layer dry weight.
 7. The medical product asclaimed in claim 1, wherein the active-ingredient-free polymer layercomprises non-amine-resistant polysiloxane polymers in which, afterpolycondensation of a resin fraction and the polydimethylsiloxanolgroups, the remaining silanol groups that are still free have not beencapped by methyl groups.
 8. The medical product as claimed in claim 1,wherein the active-ingredient-free polymer layer comprises 0 to 4% (w/w)of silicone oil, based on the layer dry weight.
 9. The medical productas claimed in claim 1, wherein the backing layer comprises an elasticfabric permeable to water.
 10. The medical product as claimed in claim1, wherein the active-ingredient-free polymer layer comprisesstyrene-isoprene-styrene block copolymers or styrene-butadiene-styreneblock copolymers in combination with hydrogenated hydrocarbon resinsand/or oils.
 11. A method for producing a medical product as claimed inclaim 1, said method comprising producing the central compartment andlining a skin-side adhesive face of said central compartment with aredetachable protective layer which protrudes on all sides by at least 4mm, classifying a patient's skin type and then, with the aid of thisclassification, selecting polymer. from a group encompassingnon-amine-resistant, highly water vapor-permeable polysiloxanes,polyacrylates or vinyl acetate-acrylate copolymers without free acidgroups or with an acid number of less than 1, polyisobutylenes,polybutylenes, styrene-isoprene-styrene block copolymers orstyrene-butadiene-styrene block copolymers or their homo- and/orcopolymers, of those polymers—and, optionally, selecting and addingadditions necessary for the medical product to be utilized for a fixingtime of at least 7 days while meeting requirements for good skincompatibility, producing coating material from said polymer and optionaladditions and coating said coating material onto an intermediate carrierand drying the coated material to form an active-ingredient-free polymerlayer/intermediate carrier laminate, laminating the backing layer ontothe active-ingredient-free polymer layer/intermediate carrier laminate,and punching out an overplaster from the foregoing laminate in a sizeand shape which overhangs the central compartment on all sides by atleast 4 mm, and adhering the overplaster, after removing theintermediate carrier, to a side of the central compartment that isfacing away from the skin-side adhesive face, such that said overplasteroverhangs the central compartment on all sides by at least 4 mm.
 12. Akit-of-parts comprising a central compartment as claimed in claim 1which is provided on its skin-side adhesive face with a redetachableprotective layer, and at least one active-ingredient-free overplasterwhich is laminated to an intermediate carrier and is comprised of a) awater vapor-permeable backing layer and b) a pressure-sensitivelyadhering, active-ingredient-free polymer layer comprisingnon-amine-resistant, highly water vapor-permeable polysiloxanes,polyacrylates or vinyl acetate-acrylate copolymers without free acidgroups or with an acid number of less than 1, polyisobutylenes,polybutylenes, styrene-isoprene-styrene block copolymers orstyrene-butadiene-styrene block copolymers or the homo- and/orcopolymers thereof, the overplaster being large enough to overhang thecentral compartment on all sides.
 13. The kit-of-parts as claimed inclaim 12, comprising at least two active-ingredient-free overplasters asclaimed in claim 12 that are laminated onto intermediate carriers, saidoverplasters differing in composition of their active-ingredient-freepolymer layers, their size and/or their shape.
 14. A kit-of-partscomprising at least two active-ingredient-free overplasters, eachoverplaster laminated onto an intermediate carrier and furthercomprising a) a water vapor-permeable backing layer and b) apressure-sensitively adhering, active-ingredient-free polymer layercomprising non-amine-resistant, highly water vapor-permeablepolysiloxanes, polyacrylates without free acid groups or with an acidnumber of less than 1, polyisobutylenes, polybutylenes,styrene-isoprene-styrene block copolymers or styrene-butadiene-styreneblock copolymers or the homo- and/or copolymers thereof, wherein, theoverplasters differ in the composition of their active-ingredient-freepolymer layers, their size and/or their shape.
 15. The kit-of-parts asclaimed in claim 12, wherein the active-ingredient-free polymer layercomprises 0 to 5% (w/w) of a neutral oil based on the layer dry weight,as compatibilizer.
 16. A medical product comprising a kit-of-parts asclaimed in claim 12, said kit comprising a central compartment and anactive-ingredient-free overplaster comprising a) a water vapor-permeablebacking layer and b) a pressure-sensitively adhering,active-ingredient-free polymer layer which is not amine-resistant andwhich comprises highly water vapor-permeable polysiloxanes,polyacrylates or vinyl acetate-acrylate copolymers without free acidgroups or with an acid number of less than 1, polyisobutylenes,polybutylenes, styrene-isoprene-styrene block copolymers orstyrene-butadiene-styrene block copolymers or the homo- and/orcopolymers thereof, wherein the central compartment ispressure-sensitively adhering and has direct skin contact after removalof the redetachable protective layer, an intermediate carrier islaminated onto the in which an active-ingredient-free overplaster, andfollowing removal of the intermediate carrier, theactive-ingredient-free overplaster is adhered to the central compartmentand overhangs the central compartment on all sides.
 17. The transdermaltherapeutic system as claim in claim 2, wherein saidactive-ingredient-free overplaster prevents the crystallization of theactive ingredient/ingredients in the active-ingredient-containingpolymer layer.
 18. The transdermal therapeutic system as claimed inclaim 2, wherein said active-ingredient-free overplaster reduces the TTScold flow.
 19. The medical product as claimed in claim 2, wherein saidseparating layer is polyester.
 20. The medical product as claimed inclaim 9, wherein the fabric is a polyester fabric.
 21. The medicalproduct as claimed in claim 10, wherein the oil is liquid paraffin. 22.A method for producing a medical product as claimed in claim 11 whereinthe patient's skin type is classified by a W. E. Roberts method.